This proposal outlines a program focused on using state-of-the-art experimental methods to address important biological problems. The immediate goal of this RCDA proposal is the development of a new high speed DNA sequencer. The realization of this instrument will allow DNA sequencing to be performed at a rate approaching one million bases per day - a rate three orders of magnitude faster than currently available techniques. To achieve this objective current DNA sequencing strategies will be combined with three new technologies to produce a low-cost, easily automated sequencing method. Laser vaporization is used to transfer tagged strands of DNA into the gas phase. Once in the gas phase resonance- enhanced, multiphoton ionization is used to place precisely one unit of positive charge on each strand and then time-of-flight mass analysis performed. The automation of the technology proposed would result in an extremely sensitive and cost effective DNA sequencing method requiring little manual labor.